Article ID Journal Published Year Pages File Type
5830291 European Journal of Pharmacology 2011 10 Pages PDF
Abstract
Colon cancer is the third most malignant neoplasm in the world and chemoprevention through dietary intervention is an emerging option to reduce its mortality. Ellagic acid (EA) a major component of berries possesses attractive biological deeds. This study is aimed to investigate the effect of ellagic acid in fostering apoptosis in 1,2-dimethyl hydrazine (DMH) mediated experimental colon carcinogenesis model. Wistar male rats were segregated into four groups: group I-control rats, group II-rats received ellagic acid (60 mg/kg body weight p.o. every day), rats in group III-induced with DMH (20 mg/kg body weight, s.c.) for 15 weeks, DMH-induced group IV rats were initiated with ellagic acid treatment. The present study is designed to explore the significance of phosphoinositide-3-kinase (PI3K)/Akt molecular pathway as well as ellagic acid's chemopreventive effect in colon cancer. DMH-induced rats exhibited elevated expressions of PI3K and Akt as confirmed by immunofluorescence, immunoblot and confocal microscopic analysis. Mechanistically, ellagic acid was found to prevent PI3K/Akt activation that in turn, results in modulation of its downstream Bcl-2 family proteins. Bax expression and caspase-3 activation was noted after ellagic acid supplementation leading to elevation of cytochrome c (cyt c) levels and finally cell death. These observations were supported by the DNA fragmentation results, which showed the occurrence of apoptosis. This study reveals the involvement of PI3K-Akt signaling through which ellagic acid induces apoptosis and subsequently suppresses colon cancer during DMH-induced rat colon carcinogenesis. In conclusion, our findings demonstrate that ellagic acid begets apoptosis in DMH-induced colon carcinoma.
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